Cancer of the gastrointestinal tract, including colorectal cancer (“CRC”), affects hundreds of thousands of individuals every year and tens of thousands of CRC-related deaths occur every year in the United States alone. See, Rustgi, 2010, “The genetics of hereditary colon cancer,” Genes & Development 21:2525-2538. CRC can arise in different ways, one of which is the transformation of adenomatous polyps into malignant tumors. Adenomatous polyposis may be inherited, as is the case for individuals with familial adenomatous polyposis (“FAP”), or it may be sporadic. Individuals with FAP or sporadic adenomatous polyposis carry mutations of the Adenomatous Polyposis Coli (“APC”) tumor suppressor gene which are associated with the formation of adenomatous polyps in the small intestine, colon and/or rectum. These polyps in turn can develop into colorectal and gastrointestinal cancer. In the case of sporadic adenomatous polyposis, a non-hereditary condition that underlies many instances of CRC, the APC gene is mutated in somatic cells. Individuals with sporadic adenomatous polyposis develop benign polyps, a subset of which may subsequently transform into malignant carcinomas.
FAP accounts for around 1% of total CRC cases and affects one in 13,000 births. Id. Mutation of APC in FAP patients is associated with the formation of hundreds to thousands of small adenomatous polyps throughout the colon. Progression of polyps to malignancy is virtually inevitable. On average, without prophylactic treatment, individuals with FAP develop CRC by age 39. Prophylactic treatment is the standard of care and involves radical surgery, including the removal of the colon, or of both the colon and the rectum, generally before the age of 25. While prophylaxis is preferable to no treatment, surgical resection of the colon (colectomy) in young patients severely impairs quality of life. In addition, surgical resection alone may be inadequate to keep patients cancer-free: patients who have colectomies have a high risk of developing polyps and cancer in the upper gastrointestinal tract. There is a serious need for effective prophylactic treatments, especially non-surgical treatments, that extend cancer-free life for individuals with FAP and individuals with sporadic adenomatous polyposis.